WO2021181645A1 - Analysis device, and flow cell securing structure - Google Patents

Analysis device, and flow cell securing structure Download PDF

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Publication number
WO2021181645A1
WO2021181645A1 PCT/JP2020/010991 JP2020010991W WO2021181645A1 WO 2021181645 A1 WO2021181645 A1 WO 2021181645A1 JP 2020010991 W JP2020010991 W JP 2020010991W WO 2021181645 A1 WO2021181645 A1 WO 2021181645A1
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Prior art keywords
flow cell
analyzer
holder
temperature
positioning pin
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PCT/JP2020/010991
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French (fr)
Japanese (ja)
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仁史 宮田
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株式会社日立ハイテク
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Priority to PCT/JP2020/010991 priority Critical patent/WO2021181645A1/en
Publication of WO2021181645A1 publication Critical patent/WO2021181645A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass

Definitions

  • This disclosure relates to an analyzer, and particularly to a flow cell installation technique used in the analyzer.
  • analyzers have proposed a method of improving throughput by immobilizing a large number of DNA fragments on a substrate and detecting a large number of DNA fragments in parallel.
  • This substrate is referred to herein as a flow cell for convenience.
  • the DNA sequence can be read by installing a flow cell in which a large number of DNA fragments are fixed in an analyzer, injecting reagents, adjusting the temperature, and detecting fluorescence.
  • the analyzer consists of a holder mechanism for installing the flow cell, a temperature control mechanism for reacting the sample in the flow cell with the reagent, a liquid feeding mechanism for injecting the reagent into the flow cell, and a detection mechanism for detecting fluorescence. It consists of a stage mechanism that moves the flow cell.
  • Patent Document 1 provides a space smaller than the flow cell size between the temperature adjusting mechanism and the holder mechanism provided around the temperature adjusting mechanism, and when the flow cell is inserted into this space, it is adjusted to the flow cell size by elastic deformation of the holder. It discloses a structure in which the flow cell presses against the temperature control surface due to the expansion of the space and the force of elastic deformation due to the expansion.
  • Patent Document 2 discloses a structure in which a flow cell is installed directly on the temperature control surface and the flow cell is pressed against the temperature control surface by a holder mechanism provided on the detection mechanism side.
  • An object of the present disclosure is to provide an analyzer that can realize miniaturization of the device by reducing the space for visual confirmation, and a flow cell fixing structure that is easy to install and replace.
  • the present disclosure includes a detection mechanism for acquiring an image of a sample, a holder mechanism for installing a flow cell on which the sample is placed, and a temperature adjustment mechanism for adjusting the temperature of the flow cell.
  • a detection mechanism for acquiring an image of a sample
  • a holder mechanism for installing a flow cell on which the sample is placed
  • a temperature adjustment mechanism for adjusting the temperature of the flow cell.
  • an analyzer comprising a flow cell insertion slot for inserting a flow cell, an insertion position for inserting the flow cell into the flow cell insertion slot, and a holding mechanism for holding the flow cell at an observation position observed by a detection mechanism.
  • a flow cell for arranging a sample and a flow cell frame for covering and protecting the flow cell are provided, the upper surface of the flow cell frame has a plurality of grooves, and a plurality of flow cell frames are provided.
  • a flow cell fixing structure capable of recognizing that the flow cell has been inserted to a predetermined position by lowering the step of the groove when the flow cell pressing claw is inserted into the holder mechanism having the flow cell pressing claw.
  • the flow cell can be installed at a position where the user can easily visually check it. Further, the space for visual confirmation that needs to be provided on the device can be reduced, so that the device can be miniaturized. Issues, configurations and effects other than those mentioned above will be clarified by the description of the following examples.
  • FIG. 1 It is a figure which shows the schematic structure of the nucleic acid analyzer in Example 1. It is explanatory drawing of the flow cell installation method in Example 1.
  • FIG. It is a perspective view of the temperature adjustment mechanism and the reagent liquid feeding part in Example 1.
  • FIG. It is an exploded view of the holder mechanism in Example 1.
  • FIG. It is explanatory drawing of the holder mechanism in Example 1.
  • FIG. It is explanatory drawing of the claw for pressing a flow cell in Example 1.
  • FIG. It is a figure explaining the structure of the holder mechanism in Example 1.
  • FIG. It is a figure explaining the structure of the flow cell in Example 1.
  • FIG. It is a figure explaining the flow cell frame in Example 1.
  • FIG. It is a figure explaining the effective utilization area in Example 1.
  • the first embodiment includes a detection mechanism for acquiring an image of a sample, a holder mechanism for installing a flow cell for arranging a sample, and a temperature adjustment mechanism for adjusting the temperature of the flow cell.
  • the holder mechanism is a flow cell insertion for inserting a flow cell. This is an example of an analyzer having a mouth, an insertion position for inserting the flow cell into the flow cell insertion port, and a holding mechanism for holding the flow cell at the observation position observed by the detection mechanism, and a flow cell fixing structure used for the device.
  • FIG. 1 is a diagram showing an overall schematic configuration of the nucleic acid analyzer of this embodiment.
  • the nucleic acid analyzer is provided in a flow cell 101 in which a flow path for flowing a reagent is formed and a large number of beads having a DNA fragment as a sample fixed therein are arranged, and in order to flow the reagent in the flow cell.
  • the reagent feeding unit 102, the temperature adjusting mechanism 103 that adjusts the temperature such as heating and cooling to promote the chemical reaction of the reagents in the flow cell, and the flow cell 101 are inserted and installed, and the flow cell 101 is further inserted into the temperature adjusting mechanism 103.
  • It is provided with a holder mechanism 104 having a function of pressing the reagent, a detection mechanism 105 for optically observing a DNA fragment in the flow cell, and a stage mechanism 106 for transporting the flow cell directly under the detection mechanism 105.
  • the holder mechanism 104 is opened to the flow cell insertion installation position by the holding mechanism described later. With the holder mechanism 104 opened at the flow cell insertion installation position, the flow cell 101 is inserted into the holder mechanism 104 and installed. After inserting and installing the flow cell, the holder mechanism 104 is tilted toward the temperature adjusting mechanism 103, and the holder mechanism 104 is moved to the observation position. Next, the stage mechanism 106 conveys the flow cell 101 directly under the detection mechanism 105, and the reagent is sent into the flow cell 101 from the reagent storage (not shown) through the reagent delivery unit 102.
  • the temperature adjusting mechanism 103 raises the temperature of the flow cell 101 to promote the chemical reaction of the reagent, and the temperature is lowered to stop the chemical reaction of the reagent, and the detection mechanism 105 observes the DNA fragment as a sample in the flow cell 101.
  • the temperature adjusting mechanism 103 has a Perche element 301 for heating and cooling the flow cell.
  • a temperature control member 302 is attached to one surface of the Pelche element, and the flow cell 101 is fixed in close contact with the upper surface of the temperature control member 302.
  • the temperature control member 302 has a built-in thermistor (not shown) for measuring its own temperature, and it is possible to control the temperature of the perche element 301 by measuring the temperature of the thermistor.
  • a heat radiating member 303 is attached to the surface of the Pelche element 301 on the opposite side of the temperature control member 302, and a heat sink 304 is attached to the end of the heat radiating member 303.
  • the heat sink 304 is cooled by a cooling means (not shown).
  • the temperature adjusting mechanism 103 has a positioning pin 305 for installing the flow cell 101 with good reproducibility.
  • the reagent liquid feeding unit 102 is attached to the temperature adjusting mechanism 103, and the reagent flowing from the reagent storage (not shown) is fed into the flow cell 101.
  • the reagent liquid feeding unit 102 has a packing 306 made of rubber or the like, and the reagent liquid feeding unit 102 and the flow path hole 804 of the flow cell 101 described later are connected via the packing 306.
  • the holder mechanism 104 of this embodiment has a torque hinge 401 as a holding mechanism.
  • This holding mechanism rotates and moves in the circumferential direction around the torque hinge 401, and the flow cell installation position, that is, the insertion position where the flow cell is inserted into the flow cell insertion port, and the detection position, that is, the flow cell is observed by the detection mechanism.
  • the holder mechanism 104 can be held at a predetermined angle at at least two positions of the observation position.
  • the observation position is at a horizontal angle with respect to the temperature adjusting mechanism 103, and the insertion position is a position 35 ° apart from the observation position.
  • the flow cell insertion position can be held by the torque hinge 401, and when the holder mechanism 104 moves to the observation position, the flow cell 101 is similarly temperature-adjusted by the force of the torque hinge 401.
  • a force in the direction of pressing against the 103 acts to prevent the flow cell from easily moving from the temperature adjusting mechanism 103.
  • the function of the torque hinge 401 as a holding mechanism is to hold the holder mechanism 104 at the flow cell insertion position and the observation position.
  • the magnet 402, the ball plunger 403, and the like are combined with the torque hinge 401.
  • it may be used as a holding mechanism in place of the torque hinge 401. That is, the holding mechanism of this embodiment can be configured by using one to three of the torque hinge, the ball plunger, and the magnet.
  • the holder mechanism 104 of this embodiment has a flow cell insertion port 501 for inserting the flow cell 101, and is a temperature control unit for bringing one side of the flow cell 101 into close contact with the temperature adjusting mechanism 103. It has a temperature control opening 502 constituting the above. Further, as shown in the lower part of the figure, it has an observation opening 503 that constitutes an observation unit for observing a DNA fragment from the opposite side of the temperature control mechanism 103 and the flow cell 101.
  • the observation unit may be covered with a member that transmits light of a desired wavelength instead of the observation opening 503.
  • the observation unit comprises an observation opening for observing the inserted flow cell, or a transmission unit made of a member that transmits light of a desired wavelength only in the observation area.
  • the flow cell 101 when the flow cell 101 is inserted into the holder mechanism 104, the flow cell 101 is installed on the holder mechanism 104 with good reproducibility on the inner side surface of the holder mechanism 104.
  • a plurality of flow cell installation claws 601 are provided.
  • the flow cell 101 can be installed with good reproducibility by being pressed against the two side surfaces of the flow cell installation claw 601 and the holder mechanism 104 by gravity. By pressing the flow cell 101 against the inner side surface of the holder mechanism, the flow cell installation claw 601 defines the flow cell installation position, and the reproducibility of the installation position can be improved.
  • the holder mechanism 104 of this embodiment has a flow cell pressing claw 602.
  • the flow cell pressing claws 602 are provided near the connection portion between the packing 306 and the flow cell 101 of the reagent liquid feeding unit 102, and at seven locations in the center of the flow cell.
  • the flow cell pressing claw 602 near the packing 306 is for efficiently crushing the packing 306.
  • the flow cell 101 when the flow cell 101 is inserted by the flow cell pressing claw 602, the flow cell 101 does not easily move in the holder mechanism 104. Further, by changing the thickness of each claw, it can be changed depending on the place where the force of the torque hinge 401 is pressed. That is, the force of pressing the flow cell 101 against the holder mechanism 104 is changed by changing the thickness of the flow cell pressing claw 602 depending on the installation position on the holder mechanism 104.
  • the flow cell pressing claw 602 in the vicinity of the packing 306 is made thicker than the flow cell pressing claw 602 in the center of the flow cell 101, so that the force of the torque hinge 401 is particularly focused on the packing 306. Since the number and thickness of the flow cell pressing claws 602 also change depending on the size of the flow cell 101 and the like, it is by no means used for a limited interpretation of the configuration of this embodiment.
  • the holder mechanism 104 of this embodiment is manufactured by being divided into three parts, a holder upper part 701, a hinge part 702, and a holder lower part 703, in order to facilitate manufacturing. There is.
  • the holder upper part 701 and the hinge part 702 are connected by a torque hinge 401, and the holder upper part 701 and the holder lower part 703 are joined by a joint portion using a screw 704 or the like.
  • the holder upper part 701 is provided with a flow cell pressing claw
  • the holder lower part 702 is provided with a protrusion near the center of the joint
  • the joint is in a state where the holder upper part is warped in the direction opposite to the reaction force of the flow cell pressing claw. Join the upper part of the holder and the lower part of the holder with.
  • the holder upper part 701 having the flow cell pressing claw 602 is the holder upper part 701 due to the reaction force of the flow cell pressing claw 602. This is because both ends may lose the reaction force and warp. Therefore, only the central portion of the holder lower component 703 is provided with the protrusion 705 on the side to which the holder upper component 701 is attached. As a result, as shown in the cross-sectional view taken along the arrow P in FIG. 7, the flow cell pressing claw 701 is bent in the direction opposite to the reaction force of the flow cell pressing claw 602 around the protrusion 705. The reaction force of 602 can be overcome and a suitable joint can be formed.
  • FIG. 8 is an exploded view showing the structure of the flow cell 101 of this embodiment.
  • the flow cell 101 is made by laminating three members of a cover glass 801, a spacer 802, and a substrate 803 having an optically transparent property, that is, light transmission.
  • the substrate 803 has a flow path hole 804.
  • the spacer 802 is generally manufactured from a material such as PDMS.
  • the thickness of the spacer 802 is 30 to 100 ⁇ m, preferably 50 ⁇ m in this embodiment.
  • the spacer 802 has a punched hole 805 for forming a flow path when the above three members are bonded together.
  • a flow path is formed by sandwiching the spacer 802 between the cover glass 801 and the substrate 803.
  • FIG. 9 includes a flow cell fixing structure according to the present embodiment, that is, a flow cell on which a sample is placed and a flow cell frame that covers and protects the flow cell.
  • the upper surface of the flow cell frame has a plurality of grooves, and the flow cell frame has a plurality of grooves.
  • An example of a flow cell fixing structure capable of recognizing that the flow cell has been inserted to a predetermined position by lowering the step of the groove when the flow cell pressing claw is inserted into a holder mechanism having a flow cell pressing claw is shown.
  • the flow cell fixing structure of this embodiment is covered with a flow cell frame 901 made of an elastic body for damage protection. Further, a recessed groove 902 is carved on the upper surface of the flow cell frame 901, and when the flow cell 101 is inserted into the holder mechanism 104, when the flow cell pressing claw 602 goes down the step of this groove, the operator's hand It can be seen that the flow cell 101 has been inserted to a fixed position with the feeling of.
  • the flow cell pressing claw 602 It is possible to determine that the flow cell has been inserted to a fixed position by falling into the recessed groove 902.
  • the flow cell frame 901 of this embodiment has a pusher 903 elastically deformed on the inner side surface.
  • the gap 904 between the flow cell 101 and the pusher 903 is smaller than the diameter of the positioning pin 305 of the temperature adjusting mechanism 103.
  • the positioning pin 305 is inserted into the gap 904.
  • the pusher 903 is elastically deformed by the difference between the diameter of the positioning pin 305 and the gap, so that the flow cell 101 is pressed against the positioning pin 305, and the flow cell 101 can be installed in the temperature adjusting mechanism 103 with high accuracy.
  • the temperature adjusting mechanism 103 includes the positioning pin 305, and the flow cell frame 901 elastically deforms to a position corresponding to the positioning pin 305, and the diameter of the positioning pin 305 formed by the gap 904 between the pusher 903 and the flow cell 101. It has a narrow hole and the holder mechanism is installed in the temperature control mechanism by inserting the positioning pin 305 into this hole.
  • the pusher 903 has a structure for improving the installation accuracy of the flow cell 101, and is not used for a limited interpretation of this embodiment.
  • the user can install the flow cell 101 with a simple operation.
  • the holder mechanism 104 moves to the flow cell insertion position so that the flow cell insertion port can be easily visually confirmed, and the installation angle makes it easy for the user to insert the flow cell.
  • the device parts and the like can be arranged in the effective utilization area 1001 extending above the holder mechanism 104 as shown in FIG. 10, so that the device can be miniaturized.

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  • Life Sciences & Earth Sciences (AREA)
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Abstract

In the present invention, there is realized an analysis device in which it is easy to perform a flow cell replacement operation, and reduction in the size of the device is made possible. The present invention comprises a detection mechanism 101 that acquires an image of a sample, a holder mechanism 104 in which is installed a flow cell for positioning the sample, and a temperature adjustment mechanism 103 that adjusts the temperature of the flow cell. The holder mechanism 104 is provided with a flow cell insertion opening for inserting the flow cell, and a holding mechanism that holds the flow cell at an insertion position for inserting the flow cell into the flow cell insertion opening and at an observation position for observing the flow cell using the detection mechanism.

Description

分析装置、及びフローセル固定構造Analyzer and flow cell fixed structure
　本開示は分析装置に関し、特に分析装置で利用するフローセルの設置技術に係る。 This disclosure relates to an analyzer, and particularly to a flow cell installation technique used in the analyzer.
　近年の分析装置では、基板上に多数のＤＮＡ断片を固定し、大量に並列検出することでスループットを向上させる方法が提案されている。この基板のことを本明細書では便宜的にフローセルと呼ぶ。 In recent years, analyzers have proposed a method of improving throughput by immobilizing a large number of DNA fragments on a substrate and detecting a large number of DNA fragments in parallel. This substrate is referred to herein as a flow cell for convenience.
　多数のＤＮＡ断片が固定されたフローセルを分析装置内に設置し、試薬の注入や温度調整を行い、蛍光等を検出することでＤＮＡ配列を読み取ることができる。分析装置の構成としては、フローセルを設置するためのホルダ機構、フローセル内の試料と試薬を反応させるための温度調整機構、試薬をフローセルに注入するための送液機構、蛍光検出を行う検出機構、フローセルを移動させるステージ機構等から成っている。 The DNA sequence can be read by installing a flow cell in which a large number of DNA fragments are fixed in an analyzer, injecting reagents, adjusting the temperature, and detecting fluorescence. The analyzer consists of a holder mechanism for installing the flow cell, a temperature control mechanism for reacting the sample in the flow cell with the reagent, a liquid feeding mechanism for injecting the reagent into the flow cell, and a detection mechanism for detecting fluorescence. It consists of a stage mechanism that moves the flow cell.
　フローセルの設置に関する公知例としては、特許文献１および特許文献２に記載された技術がある。特許文献１は、温度調整機構と温度調整機構周辺に設けられたホルダ機構との間にフローセルサイズより小さな空間を設け、フローセルをこの空間に挿入する際、ホルダの弾性変形によりフローセルサイズに合わせて空間が広がり、広がった分の弾性変形の力によりフローセルが温調調整面に押し付ける構造を開示している。特許文献２は、温度調整面に直接フローセルを設置し、検出機構側に設けられたホルダ機構により温調面にフローセルを押し付ける構造を開示している。 Known examples of the installation of the flow cell include the techniques described in Patent Document 1 and Patent Document 2. Patent Document 1 provides a space smaller than the flow cell size between the temperature adjusting mechanism and the holder mechanism provided around the temperature adjusting mechanism, and when the flow cell is inserted into this space, it is adjusted to the flow cell size by elastic deformation of the holder. It discloses a structure in which the flow cell presses against the temperature control surface due to the expansion of the space and the force of elastic deformation due to the expansion. Patent Document 2 discloses a structure in which a flow cell is installed directly on the temperature control surface and the flow cell is pressed against the temperature control surface by a holder mechanism provided on the detection mechanism side.
特開２０１１－２４２３４８号公報Japanese Unexamined Patent Publication No. 2011-242348 国際公開ＷＯ２０１５－１５１７３８International release WO2015-151738
　しかしながら、特許文献１および特許文献２に記載の技術においては、フローセルを設置の際に目視にて厳密にフローセルを設置しなければならず煩雑である。また、フローセルを設置する際にフローセル設置箇所を目視確認できるよう、装置上に目視確認用のスペースを設ける必要があり装置小型化が困難であった。 However, in the techniques described in Patent Document 1 and Patent Document 2, when the flow cell is installed, the flow cell must be installed strictly visually, which is complicated. Further, when installing the flow cell, it is necessary to provide a space for visual confirmation on the device so that the location where the flow cell is installed can be visually confirmed, which makes it difficult to miniaturize the device.
　本開示の目的は、目視確認用のスペースを減らすことで装置の小型化を実現することが可能な分析装置、並びに設置、交換作業が容易なフローセル固定構造を提供することにある。 An object of the present disclosure is to provide an analyzer that can realize miniaturization of the device by reducing the space for visual confirmation, and a flow cell fixing structure that is easy to install and replace.
　上記の目的を達成するため、本開示においては、試料の画像を取得する検出機構と、試料を配置するフローセルを設置するホルダ機構と、フローセルの温度調整を行う温度調整機構とを備え、ホルダ機構は、フローセルを挿入するフローセル挿入口と、フローセルをフローセル挿入口に挿入する挿入位置、及び検出機構で観察する観察位置に保持する保持機構と、を備える分析装置を提供する。 In order to achieve the above object, the present disclosure includes a detection mechanism for acquiring an image of a sample, a holder mechanism for installing a flow cell on which the sample is placed, and a temperature adjustment mechanism for adjusting the temperature of the flow cell. Provides an analyzer comprising a flow cell insertion slot for inserting a flow cell, an insertion position for inserting the flow cell into the flow cell insertion slot, and a holding mechanism for holding the flow cell at an observation position observed by a detection mechanism.
　また、上記の目的を達成するため、本開示においては、試料を配置するフローセルと、フローセルを覆って保護するフローセルフレームとを備え、フローセルフレームの上面は複数の溝を有し、フローセルフレームが複数のフローセル押し付け用爪を有するホルダ機構に挿入される際に、フローセル押し付け用爪が溝の段差を下ることによりフローセルが所定位置まで挿入されたことが認識できるフローセル固定構造を提供する。 Further, in order to achieve the above object, in the present disclosure, a flow cell for arranging a sample and a flow cell frame for covering and protecting the flow cell are provided, the upper surface of the flow cell frame has a plurality of grooves, and a plurality of flow cell frames are provided. Provided is a flow cell fixing structure capable of recognizing that the flow cell has been inserted to a predetermined position by lowering the step of the groove when the flow cell pressing claw is inserted into the holder mechanism having the flow cell pressing claw.
　本開示によれば、ユーザが目視確認しやすい位置でフローセルを設置することができる。更に、装置上に設ける必要がある目視確認用のスペースを減らすことができるため装置小型化が可能である。上記した以外の課題、構成及び効果は、以下の実施例の説明により明らかにされる。 According to the present disclosure, the flow cell can be installed at a position where the user can easily visually check it. Further, the space for visual confirmation that needs to be provided on the device can be reduced, so that the device can be miniaturized. Issues, configurations and effects other than those mentioned above will be clarified by the description of the following examples.
実施例１における核酸分析装置の一概略構成を示す図である。It is a figure which shows the schematic structure of the nucleic acid analyzer in Example 1. 実施例１におけるフローセル設置方法の説明図である。It is explanatory drawing of the flow cell installation method in Example 1. FIG. 実施例１における温度調整機構および試薬送液部の斜視図である。It is a perspective view of the temperature adjustment mechanism and the reagent liquid feeding part in Example 1. FIG. 実施例１におけるホルダ機構の分解図である。It is an exploded view of the holder mechanism in Example 1. FIG. 実施例１におけるホルダ機構の説明図である。It is explanatory drawing of the holder mechanism in Example 1. FIG. 実施例１におけるフローセル押し付け用の爪の説明図である。It is explanatory drawing of the claw for pressing a flow cell in Example 1. FIG. 実施例１におけるホルダ機構の構成を説明する図である。It is a figure explaining the structure of the holder mechanism in Example 1. FIG. 実施例１におけるフローセルの構成を説明する図である。It is a figure explaining the structure of the flow cell in Example 1. FIG. 実施例１におけるフローセルフレームを説明する図である。It is a figure explaining the flow cell frame in Example 1. FIG. 実施例１における有効活用エリアを説明する図である。It is a figure explaining the effective utilization area in Example 1. FIG.
　以下、添付図面を参照して本発明の実施形態について説明する。なお、添付図面は原理に則った具体的な実施例を示しているが、これらはより良い理解のためのものであり、決して限定的に解釈するために用いられるものではない。また以下の説明において、分析装置として、具体的に試料としてのＤＮＡあるいはＲＮＡ等の核酸の塩基配列を解読するための核酸分析装置を例示して説明するが、それに限定されるものではない。 Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. Although the attached drawings show concrete examples based on the principle, these are for better understanding and are not used for limited interpretation. Further, in the following description, as an analyzer, a nucleic acid analyzer for decoding a base sequence of a nucleic acid such as DNA or RNA as a sample will be specifically described, but the present invention is not limited thereto.
  実施例１は、試料の画像を取得する検出機構と、試料を配置するフローセルを設置するホルダ機構と、フローセルの温度調整を行う温度調整機構とを備え、ホルダ機構は、フローセルを挿入するフローセル挿入口と、フローセルをフローセル挿入口に挿入する挿入位置、及び検出機構で観察する観察位置に保持する保持機構と、を備える分析装置、及び装置に用いるフローセル固定構造の実施例である。 The first embodiment includes a detection mechanism for acquiring an image of a sample, a holder mechanism for installing a flow cell for arranging a sample, and a temperature adjustment mechanism for adjusting the temperature of the flow cell. The holder mechanism is a flow cell insertion for inserting a flow cell. This is an example of an analyzer having a mouth, an insertion position for inserting the flow cell into the flow cell insertion port, and a holding mechanism for holding the flow cell at the observation position observed by the detection mechanism, and a flow cell fixing structure used for the device.
　図１は、本実施例の核酸分析装置の全体概略構成を示す図である。同図において、核酸分析装置は、試薬を流すための流路が形成され、その内部に試料であるＤＮＡ断片を固定した多数のビーズを配置したフローセル１０１と、フローセル内に試薬を流すために設けられた試薬送液部１０２と、フローセル内の試薬の化学反応を促すため加熱、冷却などの温度調整を行う温度調整機構１０３と、フローセル１０１を挿入、設置し、さらに温度調整機構１０３にフローセル１０１を押し付ける機能を持つホルダ機構１０４と、フローセル内のＤＮＡ断片を光学的に観察する検出機構１０５と、検出機構１０５の直下にフローセルを搬送するステージ機構１０６とを備える。 FIG. 1 is a diagram showing an overall schematic configuration of the nucleic acid analyzer of this embodiment. In the figure, the nucleic acid analyzer is provided in a flow cell 101 in which a flow path for flowing a reagent is formed and a large number of beads having a DNA fragment as a sample fixed therein are arranged, and in order to flow the reagent in the flow cell. The reagent feeding unit 102, the temperature adjusting mechanism 103 that adjusts the temperature such as heating and cooling to promote the chemical reaction of the reagents in the flow cell, and the flow cell 101 are inserted and installed, and the flow cell 101 is further inserted into the temperature adjusting mechanism 103. It is provided with a holder mechanism 104 having a function of pressing the reagent, a detection mechanism 105 for optically observing a DNA fragment in the flow cell, and a stage mechanism 106 for transporting the flow cell directly under the detection mechanism 105.
　図２を用いて、本実施例の核酸分析装置の動作を説明する。同図において、太矢印は動作の流れを示している。まず、後で説明する保持機構により、ホルダ機構１０４をフローセル挿入設置位置まで開く。ホルダ機構１０４がフローセル挿入設置位置に開かれた状態において、フローセル１０１をホルダ機構１０４に挿入して設置する。フローセル挿入設置後、ホルダ機構１０４を温度調整機構１０３側に倒し、ホルダ機構１０４を観察位置に移動させる。次にステージ機構１０６が検出機構１０５直下にフローセル１０１を搬送し、図示せぬ試薬保管庫より試薬は試薬送液部１０２を通りフローセル１０１内に送液する。その後、温度調整機構１０３によりフローセル１０１の温度を上げ、試薬の化学反応を促し、温度を下げることで試薬の化学反応を止め、検出機構１０５によってフローセル１０１内の試料であるＤＮＡ断片を観察する。 The operation of the nucleic acid analyzer of this embodiment will be described with reference to FIG. In the figure, the thick arrow indicates the flow of operation. First, the holder mechanism 104 is opened to the flow cell insertion installation position by the holding mechanism described later. With the holder mechanism 104 opened at the flow cell insertion installation position, the flow cell 101 is inserted into the holder mechanism 104 and installed. After inserting and installing the flow cell, the holder mechanism 104 is tilted toward the temperature adjusting mechanism 103, and the holder mechanism 104 is moved to the observation position. Next, the stage mechanism 106 conveys the flow cell 101 directly under the detection mechanism 105, and the reagent is sent into the flow cell 101 from the reagent storage (not shown) through the reagent delivery unit 102. After that, the temperature adjusting mechanism 103 raises the temperature of the flow cell 101 to promote the chemical reaction of the reagent, and the temperature is lowered to stop the chemical reaction of the reagent, and the detection mechanism 105 observes the DNA fragment as a sample in the flow cell 101.
　図３～図５に本実施例の分析装置の温度調整機構１０３、試薬送液部１０２、ホルダ機構１０４、フローセル１０１の詳細構造を示す。
  図３に示すように、温度調整機構１０３はフローセルを加熱、冷却するためのペルチェ素子３０１を有している。ペルチェ素子の一面には温調部材３０２が取り付けられており、フローセル１０１は温調部材３０２の上面に密着された状態で固定される。ここで温調部材３０２には自身の温度を測定するための図示を省略したサーミスタが内蔵されており、サーミスタの温度を計測することでペルチェ素子３０１の温度を制御することが可能となる。またペルチェ素子３０１の温調部材３０２の反対側の面には、放熱部材３０３が取り付けられており、さらに放熱部材３０３の端部にはヒートシンク３０４が取り付けられている。ヒートシンク３０４は図示せぬ冷却手段によって冷却される。また温度調整機構１０３はフローセル１０１を再現性良く設置するための位置決めピン３０５を有する。 3 to 5 show the detailed structures of the temperature adjusting mechanism 103, the reagent feeding unit 102, the holder mechanism 104, and the flow cell 101 of the analyzer of this embodiment.
As shown in FIG. 3, the temperature adjusting mechanism 103 has a Perche element 301 for heating and cooling the flow cell. A temperature control member 302 is attached to one surface of the Pelche element, and the flow cell 101 is fixed in close contact with the upper surface of the temperature control member 302. Here, the temperature control member 302 has a built-in thermistor (not shown) for measuring its own temperature, and it is possible to control the temperature of the perche element 301 by measuring the temperature of the thermistor. A heat radiating member 303 is attached to the surface of the Pelche element 301 on the opposite side of the temperature control member 302, and a heat sink 304 is attached to the end of the heat radiating member 303. The heat sink 304 is cooled by a cooling means (not shown). Further, the temperature adjusting mechanism 103 has a positioning pin 305 for installing the flow cell 101 with good reproducibility.
　試薬送液部１０２は温度調整機構１０３に取り付けられており、図示せぬ試薬保管庫より流れてきた試薬をフローセル１０１内に送液する。試薬送液部１０２はゴム等で製作されたパッキン３０６を有しており、パッキン３０６を介して試薬送液部１０２と後述するフローセル１０１の流路穴８０４が接続される。 The reagent liquid feeding unit 102 is attached to the temperature adjusting mechanism 103, and the reagent flowing from the reagent storage (not shown) is fed into the flow cell 101. The reagent liquid feeding unit 102 has a packing 306 made of rubber or the like, and the reagent liquid feeding unit 102 and the flow path hole 804 of the flow cell 101 described later are connected via the packing 306.
　図４の分解図に示すように、本実施例のホルダ機構１０４は、保持機構としてトルクヒンジ４０１を有している。この保持機構は、トルクヒンジ４０１を中心として円周方向に回転し移動し、フローセル設置位置、すなわちフローセルをフローセル挿入口に挿入する挿入位置、および検出位置、すなわち、フローセルを検出機構で観察するための観察位置の少なくとも２箇所の位置において、ホルダ機構１０４を所定角度で保持することができる構造となっている。観察位置は温度調整機構１０３に対して水平の角度であり、挿入位置は観察位置から３５°開いた位置となっている。これらの所定角度は装置構成、配置に依存するものでありこの限りではない。 As shown in the exploded view of FIG. 4, the holder mechanism 104 of this embodiment has a torque hinge 401 as a holding mechanism. This holding mechanism rotates and moves in the circumferential direction around the torque hinge 401, and the flow cell installation position, that is, the insertion position where the flow cell is inserted into the flow cell insertion port, and the detection position, that is, the flow cell is observed by the detection mechanism. The holder mechanism 104 can be held at a predetermined angle at at least two positions of the observation position. The observation position is at a horizontal angle with respect to the temperature adjusting mechanism 103, and the insertion position is a position 35 ° apart from the observation position. These predetermined angles depend on the device configuration and arrangement, and are not limited to this.
　ホルダ機構１０４がフローセル挿入位置に移動した際は、トルクヒンジ４０１によりフローセル挿入位置を保持することができ、また観察位置に移動した際は、同様にトルクヒンジ４０１の力によりフローセル１０１を温度調整機構１０３に押し付ける方向の力が働き、フローセルが容易に温度調整機構１０３から動かないようにすることができる。ここでは保持機構としてのトルクヒンジ４０１の機能で、フローセル挿入位置および観察位置にホルダ機構１０４を保持しているが、図４に示すように、マグネット４０２やボールプランジャ４０３等をトルクヒンジ４０１と一緒に、或いはトルクヒンジ４０１に代わる保持機構として使用してもよい。すなわち、本実施例の保持機構は、トルクヒンジ、ボールプランジャ、マグネット（磁石）の内、１つから３つを使って構成することができる。 When the holder mechanism 104 moves to the flow cell insertion position, the flow cell insertion position can be held by the torque hinge 401, and when the holder mechanism 104 moves to the observation position, the flow cell 101 is similarly temperature-adjusted by the force of the torque hinge 401. A force in the direction of pressing against the 103 acts to prevent the flow cell from easily moving from the temperature adjusting mechanism 103. Here, the function of the torque hinge 401 as a holding mechanism is to hold the holder mechanism 104 at the flow cell insertion position and the observation position. As shown in FIG. 4, the magnet 402, the ball plunger 403, and the like are combined with the torque hinge 401. Alternatively, it may be used as a holding mechanism in place of the torque hinge 401. That is, the holding mechanism of this embodiment can be configured by using one to three of the torque hinge, the ball plunger, and the magnet.
　また図５の上段に示すように、本実施例のホルダ機構１０４はフローセル１０１を挿入するフローセル挿入口５０１を有しており、フローセル１０１の片面を温度調整機構１０３に密着するための温調部を構成する温調用開口部５０２を有する。更に同図の下段に示すように、温調調整機構１０３とフローセル１０１を挟んだ反対側からＤＮＡ断片を観察する観察部を構成する観察用開口部５０３を有する。観察部は観察用開口部５０３の代わりに所望の波長の光を透過する部材で覆った構成でもよい。言い換えるなら、観察部は、挿入したフローセルを観察するための観察用開口部、もしくは観察するエリアのみ所望の波長の光を透過する部材で製作された透過部からなる。 Further, as shown in the upper part of FIG. 5, the holder mechanism 104 of this embodiment has a flow cell insertion port 501 for inserting the flow cell 101, and is a temperature control unit for bringing one side of the flow cell 101 into close contact with the temperature adjusting mechanism 103. It has a temperature control opening 502 constituting the above. Further, as shown in the lower part of the figure, it has an observation opening 503 that constitutes an observation unit for observing a DNA fragment from the opposite side of the temperature control mechanism 103 and the flow cell 101. The observation unit may be covered with a member that transmits light of a desired wavelength instead of the observation opening 503. In other words, the observation unit comprises an observation opening for observing the inserted flow cell, or a transmission unit made of a member that transmits light of a desired wavelength only in the observation area.
　図６のホルダ機構１０４の分解図に示すように、フローセル１０１がホルダ機構１０４に挿入された際、フローセル１０１がホルダ機構１０４に再現性よく設置されるよう、ホルダ機構１０４の内部の側面には、複数のフローセル設置爪６０１が設けられている。フローセル１０１は、同図に示すようにフローセル設置爪６０１、更には重力により、ホルダ機構１０４の２つの側面に押し付けられることで再現性よく設置できる。フローセル設置爪６０１がフローセル１０１をホルダ機構の内部の側面に押し付けることで、フローセル設置位置を規定し、設置位置の再現性を向上できる。 As shown in the exploded view of the holder mechanism 104 of FIG. 6, when the flow cell 101 is inserted into the holder mechanism 104, the flow cell 101 is installed on the holder mechanism 104 with good reproducibility on the inner side surface of the holder mechanism 104. , A plurality of flow cell installation claws 601 are provided. As shown in the figure, the flow cell 101 can be installed with good reproducibility by being pressed against the two side surfaces of the flow cell installation claw 601 and the holder mechanism 104 by gravity. By pressing the flow cell 101 against the inner side surface of the holder mechanism, the flow cell installation claw 601 defines the flow cell installation position, and the reproducibility of the installation position can be improved.
　また、本実施例のホルダ機構１０４はフローセル押し付け用爪６０２を有する。これによりトルクヒンジ４０１の力をフローセル１０１の決められた位置に伝えられる。本実施例ではフローセル押し付け用爪６０２は試薬送液部１０２が有するパッキン３０６とフローセル１０１との接続部近傍、およびフローセル中央の７か所に設けている。パッキン３０６近傍のフローセル押し付け用爪６０２はパッキン３０６を効率よく潰すためであり、フローセル１０１の中央部のフローセル押し付け用爪６０２はパッキン３０６近傍だけにトルクヒンジ４０１の力を伝えると、フローセル中央が反ってしまう可能性があるため設けられている。さらにフローセル押し付け用爪６０２によりフローセル１０１を挿入した際にフローセル１０１がホルダ機構１０４内で容易に動かないようになっている。また各爪の厚みを変更することで、トルクヒンジ４０１の力を押し付ける場所により可変できるようになっている。すなわち、フローセル押し付け用爪６０２はホルダ機構１０４への設置位置により厚みを異ならせることにより、フローセル１０１をホルダ機構１０４に押し付ける力を変化させる。 Further, the holder mechanism 104 of this embodiment has a flow cell pressing claw 602. As a result, the force of the torque hinge 401 is transmitted to the determined position of the flow cell 101. In this embodiment, the flow cell pressing claws 602 are provided near the connection portion between the packing 306 and the flow cell 101 of the reagent liquid feeding unit 102, and at seven locations in the center of the flow cell. The flow cell pressing claw 602 near the packing 306 is for efficiently crushing the packing 306. When the flow cell pressing claw 602 in the center of the flow cell 101 transmits the force of the torque hinge 401 only to the vicinity of the packing 306, the center of the flow cell warps. It is provided because there is a possibility that it will end up. Further, when the flow cell 101 is inserted by the flow cell pressing claw 602, the flow cell 101 does not easily move in the holder mechanism 104. Further, by changing the thickness of each claw, it can be changed depending on the place where the force of the torque hinge 401 is pressed. That is, the force of pressing the flow cell 101 against the holder mechanism 104 is changed by changing the thickness of the flow cell pressing claw 602 depending on the installation position on the holder mechanism 104.
　本実施例ではパッキン３０６近傍のフローセル押し付け用爪６０２をフローセル１０１中央部のフローセル押し付け用爪６０２より厚くすることで特にパッキン３０６部に重点的にトルクヒンジ４０１の力が加わるようになっている。フローセル押し付け用爪６０２の数や厚みなどはフローセル１０１のサイズ等によりも変わることから、決して本実施例の構成を限定的に解釈するために用いられるものではない。 In this embodiment, the flow cell pressing claw 602 in the vicinity of the packing 306 is made thicker than the flow cell pressing claw 602 in the center of the flow cell 101, so that the force of the torque hinge 401 is particularly focused on the packing 306. Since the number and thickness of the flow cell pressing claws 602 also change depending on the size of the flow cell 101 and the like, it is by no means used for a limited interpretation of the configuration of this embodiment.
　また図７の左側の分解図に示すように、本実施例のホルダ機構１０４は製造を容易にするためホルダ上部品７０１、ヒンジ部品７０２、ホルダ下部品７０３の３部品に分けられて製作されている。ホルダ上部品７０１とヒンジ部品７０２はトルクヒンジ４０１により接続され、ホルダ上部品７０１とホルダ下部品７０３はねじ７０４等を用いた接合部により接合される。ホルダ上部品７０１はフローセル押し付け用爪を備え、ホルダ下部品７０２は接合部の中央付近に突起を備え、接合部は、フローセル押し付け用爪の反力とは逆向きにホルダ上部品を反らせた状態でホルダ上部品と前記ホルダ下部品を接合する。 Further, as shown in the exploded view on the left side of FIG. 7, the holder mechanism 104 of this embodiment is manufactured by being divided into three parts, a holder upper part 701, a hinge part 702, and a holder lower part 703, in order to facilitate manufacturing. There is. The holder upper part 701 and the hinge part 702 are connected by a torque hinge 401, and the holder upper part 701 and the holder lower part 703 are joined by a joint portion using a screw 704 or the like. The holder upper part 701 is provided with a flow cell pressing claw, the holder lower part 702 is provided with a protrusion near the center of the joint, and the joint is in a state where the holder upper part is warped in the direction opposite to the reaction force of the flow cell pressing claw. Join the upper part of the holder and the lower part of the holder with.
　これは、ねじ留めによる接合部はスペースの問題から図示のように４箇所留められているが、フローセル押し付け用爪６０２をもつホルダ上部品７０１はフローセル押し付け用爪６０２の反力によりホルダ上部品７０１両端が反力に負け反ってしまう可能性があるためである。そのため、ホルダ下部品７０３の中央部のみホルダ上部品７０１が取り付く側に突起７０５を持たせている。これにより、図７のＰ矢視方向の矢視断面図に示すように、突起７０５を中心としてフローセル押し付け用爪６０２の反力とは逆向きにホルダ上部品７０１を反らせることでフローセル押し付け用爪６０２の反力に打ち勝つことができ、好適な接合部を形成できる。 This is because the joints by screwing are fastened at four places as shown in the figure due to space problems, but the holder upper part 701 having the flow cell pressing claw 602 is the holder upper part 701 due to the reaction force of the flow cell pressing claw 602. This is because both ends may lose the reaction force and warp. Therefore, only the central portion of the holder lower component 703 is provided with the protrusion 705 on the side to which the holder upper component 701 is attached. As a result, as shown in the cross-sectional view taken along the arrow P in FIG. 7, the flow cell pressing claw 701 is bent in the direction opposite to the reaction force of the flow cell pressing claw 602 around the protrusion 705. The reaction force of 602 can be overcome and a suitable joint can be formed.
　図８は、本実施例のフローセル１０１の構造を示す分解図である。フローセル１０１は、光学的に透明な特性すなわち光透過性を有するカバーガラス８０１、スペーサ８０２、及び、基板８０３の３つの部材を張り合わせて作製される。基板８０３は、流路穴８０４を有する。スペーサ８０２は、ＰＤＭＳなどの素材より製造されることが一般的である。スペーサ８０２の厚さは３０～１００μｍであり、本実施例では好適には５０μｍである。また、スペーサ８０２は、上記３つの部材を貼り合わせたときに流路を形成するための打ち抜き穴８０５を有する。スペーサ８０２をカバーガラス８０１及び基板８０３で挟みこむことにより、流路が形成される。 FIG. 8 is an exploded view showing the structure of the flow cell 101 of this embodiment. The flow cell 101 is made by laminating three members of a cover glass 801, a spacer 802, and a substrate 803 having an optically transparent property, that is, light transmission. The substrate 803 has a flow path hole 804. The spacer 802 is generally manufactured from a material such as PDMS. The thickness of the spacer 802 is 30 to 100 μm, preferably 50 μm in this embodiment. Further, the spacer 802 has a punched hole 805 for forming a flow path when the above three members are bonded together. A flow path is formed by sandwiching the spacer 802 between the cover glass 801 and the substrate 803.
　図９は、本実施例におけるフローセル固定構造、すなわち、試料を配置するフローセルと、フローセルを覆って保護するフローセルフレームとを備え、フローセルフレームの上面は複数の溝を有し、フローセルフレームが複数のフローセル押し付け用爪を有するホルダ機構に挿入される際に、フローセル押し付け用爪が溝の段差を下ることによりフローセルが所定位置まで挿入されたことが認識できるフローセル固定構造の一例を示す。 FIG. 9 includes a flow cell fixing structure according to the present embodiment, that is, a flow cell on which a sample is placed and a flow cell frame that covers and protects the flow cell. The upper surface of the flow cell frame has a plurality of grooves, and the flow cell frame has a plurality of grooves. An example of a flow cell fixing structure capable of recognizing that the flow cell has been inserted to a predetermined position by lowering the step of the groove when the flow cell pressing claw is inserted into a holder mechanism having a flow cell pressing claw is shown.
　すなわち、同図に示すように、本実施例のフローセル固定構造は破損保護のため、弾性体で製作されたフローセルフレーム９０１にて覆われた構成になっている。また、フローセルフレーム９０１の上面には窪んだ溝９０２が彫られており、フローセル１０１をホルダ機構１０４に挿入した際に、フローセル押し付け用爪６０２がこの溝の段差を下る際に、操作者の手の感覚でフローセル１０１が定位置まで挿入されたことが分かるようになっている。このように、フローセルを保護するフローセルフレームの上面のフローセル押し付け用爪６０２に対応する位置に溝を備え、フローセル１０１を覆ったフローセルフレーム９０１をホルダ機構１０４に設置した際に、フローセル押し付け用爪６０２が窪んだ溝９０２に落ちることにより、フローセルが定位置まで挿入されたことを判別可能とすることができる。 That is, as shown in the figure, the flow cell fixing structure of this embodiment is covered with a flow cell frame 901 made of an elastic body for damage protection. Further, a recessed groove 902 is carved on the upper surface of the flow cell frame 901, and when the flow cell 101 is inserted into the holder mechanism 104, when the flow cell pressing claw 602 goes down the step of this groove, the operator's hand It can be seen that the flow cell 101 has been inserted to a fixed position with the feeling of. As described above, when the flow cell frame 901 having a groove at the position corresponding to the flow cell pressing claw 602 on the upper surface of the flow cell frame that protects the flow cell and covering the flow cell 101 is installed in the holder mechanism 104, the flow cell pressing claw 602 It is possible to determine that the flow cell has been inserted to a fixed position by falling into the recessed groove 902.
　更に、本実施例のフローセルフレーム９０１は内側側面に弾性変形するプッシャ９０３を持つ。フローセル１０１とプッシャ９０３の隙間９０４は、温度調整機構１０３が有する位置決めピン３０５の直径より小さくなっている。フローセル１０１をホルダ機構１０４に挿入した後、ホルダ機構１０４を観察位置に移動すると、この隙間９０４に位置決めピン３０５が挿入される。プッシャ９０３は位置決めピン３０５の直径と隙間の差分だけ弾性変形することでフローセル１０１は位置決めピン３０５に押し付けられ、フローセル１０１を精度よく温度調整機構１０３に設置できる。 Further, the flow cell frame 901 of this embodiment has a pusher 903 elastically deformed on the inner side surface. The gap 904 between the flow cell 101 and the pusher 903 is smaller than the diameter of the positioning pin 305 of the temperature adjusting mechanism 103. After inserting the flow cell 101 into the holder mechanism 104, when the holder mechanism 104 is moved to the observation position, the positioning pin 305 is inserted into the gap 904. The pusher 903 is elastically deformed by the difference between the diameter of the positioning pin 305 and the gap, so that the flow cell 101 is pressed against the positioning pin 305, and the flow cell 101 can be installed in the temperature adjusting mechanism 103 with high accuracy.
　すなわち、温度調整機構１０３は位置決めピン３０５を備え、フローセルフレーム９０１は位置決めピン３０５に対応する位置に弾性変形するプッシャ９０３、及びプッシャ９０３とフローセル１０１の隙間９０４により構成された位置決めピン３０５の直径より狭い穴を備え、ホルダ機構はこの穴に位置決めピン３０５を挿入することにより、温度調整機構に設置される。なお、プッシャ９０３に関してはあくまでフローセル１０１の設置精度を上げる構造であり本実施例を限定的に解釈するために用いられるものではない。 That is, the temperature adjusting mechanism 103 includes the positioning pin 305, and the flow cell frame 901 elastically deforms to a position corresponding to the positioning pin 305, and the diameter of the positioning pin 305 formed by the gap 904 between the pusher 903 and the flow cell 101. It has a narrow hole and the holder mechanism is installed in the temperature control mechanism by inserting the positioning pin 305 into this hole. The pusher 903 has a structure for improving the installation accuracy of the flow cell 101, and is not used for a limited interpretation of this embodiment.
　以上詳述したように、本実施例の分析装置、フローセル固定構造によればユーザは容易な動作でフローセル１０１を設置できる。フローセル１０１取り付けの際は、ホルダ機構１０４がフローセル挿入位置に移動することでフローセル挿入口が目視確認しやすく、またユーザにとってフローセルを挿入しやすい設置角度となる。 As described in detail above, according to the analyzer and flow cell fixing structure of this embodiment, the user can install the flow cell 101 with a simple operation. When the flow cell 101 is attached, the holder mechanism 104 moves to the flow cell insertion position so that the flow cell insertion port can be easily visually confirmed, and the installation angle makes it easy for the user to insert the flow cell.
　フローセル挿入の際ユーザはフローセル挿入口のみ目視確認できれば良いため、従来のような目視確認のための大きなスペースは必要ない。その結果、図１０に示すようなホルダ機構１０４の上部に広がる有効活用エリア１００１に、装置部品等を配置することが可能となるため、装置の小型化が可能である。 When inserting the flow cell, the user only needs to be able to visually check the flow cell insertion slot, so there is no need for a large space for visual confirmation as in the past. As a result, the device parts and the like can be arranged in the effective utilization area 1001 extending above the holder mechanism 104 as shown in FIG. 10, so that the device can be miniaturized.
　本開示は上記した実施例に限定されるものではなく、様々な変形例が含まれる。例えば、上記した実施例は本開示のより良い理解のために詳細に説明したのであり、必ずしも説明した全ての構成を備えるものに限定されるものではない。 The present disclosure is not limited to the above-described embodiment, and includes various modified examples. For example, the above embodiments have been described in detail for a better understanding of the present disclosure and are not necessarily limited to those comprising all of the described configurations.
１０１　フローセル
１０２　試薬送液部
１０３　温度調整機構
１０４　ホルダ機構
１０５　検出機構
１０６　ステージ機構
３０１　ホルダ機構
３０２　温調部材
３０３　放熱部材
３０４　ヒートシンク
３０５　位置決めピン
３０６　パッキン
４０１　トルクヒンジ
４０２　マグネット
４０３　ボールプランジャ
５０１　フローセル挿入口
５０２　温調用開口部
５０３　観察用開口部
６０１　フローセル設置爪
６０２　フローセル押し付け用爪
７０１　ホルダ上部品
７０２　ヒンジ部品
７０３　ホルダ下部品
７０４　ねじ
７０５　突起
８０１　カバーガラス
８０２　スペーサ
８０３　基板
８０４　流路穴
８０５　打ち抜き穴
９０１　フローセルフレーム
９０２　溝
９０３　プッシャ
９０４　隙間
１００１　有効活用エリア 101 Flow cell 102 Reagent liquid delivery unit 103 Temperature adjustment mechanism 104 Holder mechanism 105 Detection mechanism 106 Stage mechanism 301 Holder mechanism 302 Temperature control member 303 Heat dissipation member 304 Heat sink 305 Positioning pin 306 Packing 401 Torque hinge 402 Magnet 403 Ball plunger 501 Flow cell insertion port 502 Temperature control opening 503 Observation opening 601 Flow cell installation claw 602 Flow cell pressing claw 701 Holder upper part 702 Hinge part 703 Holder lower part 704 Screw 705 Protrusion 801 Cover glass 802 Spacer 803 Board 804 Channel hole 805 Punch hole 901 Flow cell frame 902 Groove 903 Pusher 904 Gap 1001 Effective utilization area

Claims (15)

  1. 分析装置であって、
    試料の画像を取得する検出機構と、前記試料を配置するフローセルを設置するホルダ機構と、前記フローセルの温度調整を行う温度調整機構とを備え、
    前記ホルダ機構は、前記フローセルを挿入するフローセル挿入口と、前記フローセルを前記フローセル挿入口に挿入する挿入位置、及び前記検出機構で観察する観察位置に保持する保持機構と、を備える、
    ことを特徴とする分析装置。     It ’s an analyzer,
    It is provided with a detection mechanism for acquiring an image of a sample, a holder mechanism for installing a flow cell on which the sample is placed, and a temperature adjustment mechanism for adjusting the temperature of the flow cell.
    The holder mechanism includes a flow cell insertion port for inserting the flow cell, an insertion position for inserting the flow cell into the flow cell insertion port, and a holding mechanism for holding the flow cell at an observation position observed by the detection mechanism.
    An analyzer characterized by this.
  2. 請求項１記載の分析装置であって、
    前記観察位置は、前記温度調整機構で前記フローセルを温度調整する位置である、
    ことを特徴とする分析装置。     The analyzer according to claim 1, wherein the analyzer
    The observation position is a position where the temperature adjustment mechanism adjusts the temperature of the flow cell.
    An analyzer characterized by this.
  3. 請求項１記載の分析装置であって、
    前記保持機構は、前記フローセル挿入口を所定角度で保持する、
    ことを特徴とする分析装置。     The analyzer according to claim 1, wherein the analyzer
    The holding mechanism holds the flow cell insertion port at a predetermined angle.
    An analyzer characterized by this.
  4. 請求項３記載の分析装置であって、
    前記保持機構は、トルクヒンジ、ボールブランジャ、あるいはマグネットの少なくとも一つを備える、
    ことを特徴とした分析装置。     The analyzer according to claim 3, wherein the analyzer
    The holding mechanism comprises at least one of a torque hinge, a ball blanger, or a magnet.
    An analyzer characterized by that.
  5. 請求項１記載の分析装置であって、
    前記ホルダ機構は、挿入した前記フローセルを前記温度調整機構に密着するための温調部と、挿入した前記フローセルを観察するための観察部を有する、
    ことを特徴とした分析装置。     The analyzer according to claim 1, wherein the analyzer
    The holder mechanism has a temperature control unit for bringing the inserted flow cell into close contact with the temperature adjusting mechanism, and an observation unit for observing the inserted flow cell.
    An analyzer characterized by that.
  6. 請求項５記載の分析装置であって、
    前記温調部は温調用開口部からなる、
    ことを特徴とした分析装置。     The analyzer according to claim 5, wherein the analyzer
    The temperature control portion is composed of a temperature control opening.
    An analyzer characterized by that.
  7. 請求項５記載の分析装置であって、
    前記観察部は、挿入した前記フローセルを観察するための観察用開口部、もしくは観察するエリアのみ所望の波長の光を透過する部材で製作された透過部からなる、
    ことを特徴とした分析装置。     The analyzer according to claim 5, wherein the analyzer
    The observation unit comprises an observation opening for observing the inserted flow cell, or a transmission unit made of a member that transmits light of a desired wavelength only in the observation area.
    An analyzer characterized by that.
  8. 請求項１記載の分析装置であって、
    前記ホルダ機構は、内側の側面にフローセル設置爪を備え、前記フローセル設置爪が前記ホルダ機構の前記フローセルの設置位置を規定する、
    ことを特徴とする分析装置。     The analyzer according to claim 1, wherein the analyzer
    The holder mechanism is provided with a flow cell installation claw on the inner side surface, and the flow cell installation claw defines the installation position of the flow cell of the holder mechanism.
    An analyzer characterized by this.
  9. 請求項１記載の分析装置であって、
    前記ホルダ機構は、前記保持機構の力を前記フローセルに伝える、複数のフローセル押し付け用爪を備える、
    ことを特徴とする分析装置。     The analyzer according to claim 1, wherein the analyzer
    The holder mechanism includes a plurality of flow cell pressing claws that transmit the force of the holding mechanism to the flow cell.
    An analyzer characterized by this.
  10. 請求項９記載の分析装置であって、
    複数の前記フローセル押し付け用爪は、前記ホルダ機構への設置位置により厚みが異なる、
    ことを特徴とする分析装置。     The analyzer according to claim 9, wherein the analyzer
    The thickness of the plurality of flow cell pressing claws varies depending on the installation position on the holder mechanism.
    An analyzer characterized by this.
  11. 請求項９記載の分析装置であって、
    前記ホルダ機構は、接合部で接合されるホルダ上部品とホルダ下部品とを含み、
    前記ホルダ上部品は前記フローセル押し付け用爪を備え、前記ホルダ下部品は前記接合部の中央付近に突起を備え、前記接合部は、前記フローセル押し付け用爪の反力とは逆向きに前記ホルダ上部品を反らせた状態で前記ホルダ上部品と前記ホルダ下部品を接合する、
    ことを特徴とする分析装置。     The analyzer according to claim 9, wherein the analyzer
    The holder mechanism includes a holder upper part and a holder lower part to be joined at a joint portion.
    The holder upper part is provided with the flow cell pressing claw, the holder lower part is provided with a protrusion near the center of the joint portion, and the joint portion is on the holder in the direction opposite to the reaction force of the flow cell pressing claw. Join the upper part of the holder and the lower part of the holder with the parts warped.
    An analyzer characterized by this.
  12. 請求項９記載の分析装置であって、
    前記フローセルを保護するフローセルフレームを備え、前記フローセルフレームの上面の前記フローセル押し付け用爪に対応する位置に溝を備える、
    ことを特徴とする分析装置。     The analyzer according to claim 9, wherein the analyzer
    A flow cell frame that protects the flow cell is provided, and a groove is provided on the upper surface of the flow cell frame at a position corresponding to the flow cell pressing claw.
    An analyzer characterized by this.
  13. 請求項１２記載の分析装置であって、
    前記温度調整機構は位置決めピンを備え、前記フローセルフレームは前記位置決めピンに対応する位置に弾性変形するプッシャ、及び前記プッシャと前記フローセルの隙間により構成された前記位置決めピンの直径より狭い穴を備え、当該穴に前記位置決めピンが挿入される、
    ことを特徴とする分析装置。     The analyzer according to claim 12, wherein the analyzer
    The temperature adjusting mechanism includes a positioning pin, and the flow cell frame includes a pusher elastically deformed to a position corresponding to the positioning pin, and a hole narrower than the diameter of the positioning pin formed by a gap between the pusher and the flow cell. The positioning pin is inserted into the hole.
    An analyzer characterized by this.
  14. フローセル固定構造であって、
    試料を配置するフローセルと、前記フローセルを覆って保護するフローセルフレームとを備え、
    前記フローセルフレームの上面に複数の溝が形成され、前記フローセルフレームが、複数のフローセル押し付け用爪を有するホルダ機構に挿入される際に、前記フローセル押し付け用爪が前記溝の段差を下ることにより前記フローセルが所定位置まで挿入されたことが認識できる、
    ことを特徴とするフローセル固定構造。     Flow cell fixed structure
    A flow cell for arranging a sample and a flow cell frame for covering and protecting the flow cell are provided.
    A plurality of grooves are formed on the upper surface of the flow cell frame, and when the flow cell frame is inserted into a holder mechanism having a plurality of flow cell pressing claws, the flow cell pressing claws descend the steps of the grooves. It can be recognized that the flow cell has been inserted to the specified position.
    A flow cell fixed structure characterized by that.
  15. 請求項１４記載のフローセル固定構造であって、
    前記フローセルフレームは、前記フローセルの温度を調整する温度調整機構の位置決めピンに対応する位置に弾性変形可能なプッシャ、及び当該プッシャと前記フローセルの隙間により構成された前記位置決めピンの径より狭い穴を有し、当該穴に前記位置決めピンを挿入することにより、前記ホルダ機構を前記温度調整機構に設置できる、
    ことを特徴とするフローセル固定構造。     The flow cell fixed structure according to claim 14, wherein the flow cell is fixed.
    The flow cell frame has a pusher elastically deformable at a position corresponding to a positioning pin of a temperature adjusting mechanism for adjusting the temperature of the flow cell, and a hole narrower than the diameter of the positioning pin formed by a gap between the pusher and the flow cell. The holder mechanism can be installed in the temperature adjusting mechanism by inserting the positioning pin into the hole.
    A flow cell fixed structure characterized by that.
PCT/JP2020/010991 2020-03-13 2020-03-13 Analysis device, and flow cell securing structure WO2021181645A1 (en)

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US4641930A (en) * 1983-12-15 1987-02-10 Micromanipulator Microscope Co., Inc. Apparatus for positioning flat objects for microscopic examination
JP2010539987A (en) * 2007-10-05 2010-12-24 アプライド バイオシステムズ， エルエルシー Biological analysis system, biological analysis apparatus, and biological analysis method
JP2011242348A (en) * 2010-05-21 2011-12-01 Hitachi High-Technologies Corp Fixing device for flow cell and dna analyzer using the same
JP2013024821A (en) * 2011-07-26 2013-02-04 Hitachi High-Technologies Corp Nucleic acid analysis reaction device
JP2015040733A (en) * 2013-08-21 2015-03-02 株式会社日立ハイテクノロジーズ Flow cell-fixing device, and nucleic acid analyzer
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Publication number Priority date Publication date Assignee Title
US4641930A (en) * 1983-12-15 1987-02-10 Micromanipulator Microscope Co., Inc. Apparatus for positioning flat objects for microscopic examination
JP2010539987A (en) * 2007-10-05 2010-12-24 アプライド バイオシステムズ， エルエルシー Biological analysis system, biological analysis apparatus, and biological analysis method
JP2011242348A (en) * 2010-05-21 2011-12-01 Hitachi High-Technologies Corp Fixing device for flow cell and dna analyzer using the same
JP2013024821A (en) * 2011-07-26 2013-02-04 Hitachi High-Technologies Corp Nucleic acid analysis reaction device
JP2015040733A (en) * 2013-08-21 2015-03-02 株式会社日立ハイテクノロジーズ Flow cell-fixing device, and nucleic acid analyzer
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